Dataset Information

Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis in vitro and in vivo.

ABSTRACT: Key metabolic enzymes regulatethe fluxes of small compounds to provide the basal substrates for cellular architecture and energy. Some of them are reported to be important carcinogenesis- and metastasis-related genes. In our work, we performed RNA-seq for50 pairs of normal-tumor of hepatocellular carcinoma (HCC) samples and found that the expression of dimethylglycine dehydrogenase (DMGDH) is decreased in HCC. The analysis of protein levels with Western blotting and immunohistochemistry also conformed our findings. It is proven to be a valuable biomarker for both diagnosis and prognosis in three independent datasets. Furthermore, we revealed that DMGDH suppresses migration, invasion and metastasis both in vitro and in vivo. By utilizing gene expression microarray for DMGDH, we identified several possible pathways altered in a DMGDH over-expressing cell line. Among these pathways, we noted that the phosphorylation of Akt-308/473 was significantly suppressed when DMGDH was over-expressed. In summary, our work reveals that DMGDH is a potential valuable biomarker for both diagnosis and prognosisfor HCC, and DMGDH gene expression suppresses metastasis through the Akt signaling pathway.

SUBMITTER: Liu G

PROVIDER: S-EPMC5078037 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis in vitro and in vivo.

Liu Gang G Hou Guojun G Li Liang L Li Yixue Y Zhou Weiping W Liu Lei L

Oncotarget 20160501 22

Key metabolic enzymes regulatethe fluxes of small compounds to provide the basal substrates for cellular architecture and energy. Some of them are reported to be important carcinogenesis- and metastasis-related genes. In our work, we performed RNA-seq for50 pairs of normal-tumor of hepatocellular carcinoma (HCC) samples and found that the expression of dimethylglycine dehydrogenase (DMGDH) is decreased in HCC. The analysis of protein levels with Western blotting and immunohistochemistry also con ...[more]

PMID: 27119355

Similar Datasets

Project description:ObjectiveHepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear.MethodsThe differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator Cox regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both bioinformatic analysis and in vitro experiments.ResultsThe level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis, and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant upregulation of p53 and the downstream PUMA and NOXA and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2.ConclusionsCDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage, and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.

Project description:BackgroundHepatocellular carcinoma (HCC) is a tumor with a high recurrence rate, poor prognosis, and rapid progression. Therefore, it is necessary to find a novel biomarker for HCC. Coiled-coil domain containing 25 (CCDC25) has been identified as a target molecule that mediates liver metastasis in colon cancer. However, the molecular mechanisms of CCDC25 in HCC are unknown. This study aimed to explore the role of CCDC25 in HCC.MethodsThe expression of CCDC25 in HCC was identified through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic curve (ROC) curves were drawn to evaluate the diagnostic value of CCDC25 for HCC. The effect of CCDC25 on the prognosis of HCC was analyzed by using the Kaplan-Meier plotter. Co-expressed genes and Gene Set Enrichment Analysis (GSEA) were used to explore the related functions and regulatory signaling pathways of CCDC25. Moreover, we employed the Tumor Immune Estimation Resource (TIMER) database and CIBERSORT algorithm to investigate the relationship between CCDC25 and the tumor immune microenvironment (TME) in HCC. Meanwhile, the effect of CCDC25 on the sensitivity of HCC patients to chemotherapy drugs was evaluated. Finally, we explored the prognostic methylation sites of CCDC25 using the MethSurv database.ResultsCCDC25 expression was low in HCC. Low CCDC25 expression was significantly associated with poor overall survival of HCC and may be comparable to the ability of AFP to diagnose HCC. Dysregulation of glucose metabolism, fatty acid metabolism, amino acid metabolism, ubiquitination modification, and apoptosis inhibition caused by CCDC25 downregulation may be the causes and results of HCC. In addition, CCDC25 was positively correlated with the infiltration level of various adaptive antitumor immune cells. The levels of immune cell infiltration and immune checkpoint expression were lower in the samples with high CCDC25 expression. What is more, we found that downregulated CCDC25 may increase the sensitivity or resistance of HCC patients to multiple drugs, including sorafenib. We also identified a methylation site for CCDC25, which may be responsible for poor prognosis and low CCDC25 expression in HCC patients. Finally, CCDC25 may be associated with HCC ferroptosis.ConclusionsCCDC25 may be a potential diagnostic and prognostic marker for HCC and is associated with immune infiltration and ferroptosis.

Dataset Information

Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis in vitro and in vivo.

Publications

Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis in vitro and in vivo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets